Background The noradrenergic neurons of locus coeruleus (LC) project to the spinal dorsal horn (SDH), and release norepinephrine (NE) to inhibit pain transmission. However, its effect on pathological pain and the cellular mechanism in the SDH remains unclear. This study aimed to explore the analgesic effects and the anti-neuroinflammation mechanism of LC-spinal cord noradrenergic pathway (LC:SC) in neuropathic pain (NP) mice with sciatic chronic constriction injury. Methods The Designer Receptors Exclusively Activated by Designer Drugs (DREADD) was used to selectively activate LC:SC. Noradrenergic neuron-specific retro–adeno-associated virus was injected to the spinal cord. Pain threshold, LC and wide dynamic range (WDR) neuron firing, neuroinflammation (microglia and astrocyte activation, cytokine expression), and α2AR expression in SDH were evaluated. Results Activation of LC:SC with DREADD increased the mechanical and thermal nociceptive thresholds and reduced the WDR neuron firing. LC:SC activation (daily, 7 days) downregulated TNF-α and IL-1β expression, upregulated IL-4 and IL-10 expression in SDH, and inhibited microglia and astrocytes activation in NP mice. Immunofluorescence double staining confirmed that LC:SC activation decreased the expression of cytokines in microglia of the SDH. In addition, the effects of LC:SC activation could be reversed by intrathecal injection of yohimbine. Immunofluorescence of SDH showed that NE receptor α2B-AR was highly expressed in microglia in CCI mice. Conclusion These findings indicate that selective activation of LC:SC alleviates NP in mice by increasing the release of NE and reducing neuroinflammation of astrocytes and microglia in SDH.

BackgroundPostherpetic neuralgia (PHN) is one kind of severe neuropathic pain which currently cannot be effectively cured. Recent researches suggest that intravenous infusion of lidocaine has a therapeutic effect on neuropathic pain such as PHN; however, the optimal dose and frequency of lidocaine infusion and the effectiveness and safety of this treatment in PHN patients still needs more clinical research. The aim of this study was to evaluate the therapeutic effects of daily intravenous lidocaine infusion on the outcome of the routine treatment of PHN.MethodsSixty PHN patients were randomly divided into two groups: 1) control group (Control), treated with conventional therapies, such as antiepileptic pills, analgesics, neurotrophic medicines, paravertebral spinal nerve block and physiotherapy; 2) lidocaine group (Lido) received daily infusion of lidocaine (4 mg/kg) besides the conventional treatments. If the pain is not controlled sufficiently, additional tramadol is given and the average consumption of tramadol is calculated. Pain intensity was assessed before and after each infusion, and the number of breakthrough pain in the last 24 hrs were recorded. The incidence of adverse reactions related to intravenous lidocaine infusion was recorded.ResultsFor five consecutive days, numeric rating scale (NRS) scores were significantly decreased after 1 hr of intravenous infusion of lidocaine. Compared with Control, the NRS scores and the frequency of breakthrough pain in the Lido were significantly reduced. In addition, the extra tramadol consumption in the Lido was significantly lower than that in the Control, and the average hospital stay of patients in Lido was decreased. However, anxiety and depression scores showed no difference between Lido and Control.ConclusionDaily intravenous lidocaine (4 mg/kg for 5 days) enhanced the outcome of PHN treatment, reduced the amount of analgesic medicine and shortened the length of hospital stay with no obvious adverse side effects.

Stellate ganglion (SG) intervention is currently widely being studied in many kinds of chronic pain. As one of the convenient ways to treat the sympathetic nervous system, the indications for stellate ganglion intervention (SGI) include complex regional pain syndrome, postherpetic neuralgia, cancer pain of different origins, orofacial pain, and so forth. SGI refers to the reversible or irreversible blocking of the cervical sympathetic trunk, cervical sympathetic ganglion, and their innervation range through noninvasive or minimally invasive treatment. Current treatment options include stellate ganglion block (SGB), SG pulsed radiofrequency, continuous radiofrequency treatment, and noninvasive SGB. In particular, SGB continues to be one of the most studied methods in chronic pain management. However, a single SGB usually provides only short-term effects; repeated SGB may result in complications such as hoarseness, light-headedness, and vessel or nerve injury. Meanwhile, the mechanism of SGI is still unclear. This review discusses the research progress of SGI methods, effectiveness, complications, and possible mechanisms in the management of chronic pain.chronic pain, pulse radiofrequency, stellate ganglion, stellate ganglion block | INTRODUCTIONChronic pain is defined as pain that persists or recurs for more than 3 months, usually accompanied by negative emotions including anxiety and/or depression. 1 Chronic pain severely affects not only physical and mental health but also places a huge economic burden on the family and society. The incidence of chronic pain is reported to be over 30% in China. 2 Current conventional methods for the treatment of chronic pain include drug therapy, minimally invasive therapy, psychotherapy, and physical therapy. 3 However, research has found that sympathetic nerves are involved in the maintenance of many kinds of chronic pain. 4 Therefore, inhibition of sympathetic hyperexcitability may improve the therapeutic effect, which may be related to the involvement of sympathetic nerves in regulating glial inflammation. 5 Among them, intervention of stellate ganglion (SG) is effective for pain in the head, face, neck, upper limbs, or upper chest. In this review, we summarize the clinical evidence available for the effectiveness of stellate ganglion intervention (SGI), and demonstrate clinical applications of SGI.

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Background: P2X4 receptor (P2X4R)-mediated spinal microglial activation makes a critical contribution to pathologically enhanced pain processing in the dorsal horn. It can be upregulated under conditions of neuropathic pain. However, the specific mechanism of pathogenesis and potential molecular targets has not yet been made explicit. MicroRNAs (miRNAs) are commonly recognized as indicators in neuropathic pain pathophysiology.Methods: We established the pain model of spared nerve injury (SNI), and the 50% paw withdrawal thresholds (PWMTs) were used to assess behavior of mouse. MiRNA expression profiling was performed to detect differential expressed miRNA. The western-bolt and quantitative real time PCR to examine P2X4R and miRNA expression in the mouse. Dual-luciferase reporter assays confirmed the correlation between P2X4R and miRNA. Fluorescence in situ hybridization was used to show location between P2X4R and miRNA. Results: In the present study, we found that P2X4R was up-regulated in the spinal dorsal horn of mice following spared nerve injury (SNI), and we identified 69 miRNAs (46 up-regulated and 23 down-regulated miRNAs) were differently expressed (fold change > 2, P < 0.05). P2X4R was a major target of miR-106b-5p (one of down-regulated miRNAs in SNI) with bioinformatics technology and quantitative real time PCR analysis validated the expressed change of miR-106b-5p, and dual-luciferase reporter assays confirmed the correlation between them. Fluorescence in situ hybridization showed that miR-106b-5p was co-localized with P2X4R in the spinal cord. Transfection with miR-106b-5p mimic on BV2 cells reversed the up-regulation of P2X4R induced by LPS. Moreover, miR-106b-5p overexpression significantly attenuated neuropathic pain induced by SNI, with decreased expression of P2X4R mRNA and protein in the spinal cord.Conclusion: Taken together, our results suggest that miR-106b-5p can serve as an important regulator of neuropathic pain development by targeting P2X4R.